Assessing Nasal Epithelial Dynamics: Impact of the Natural Nasal Cycle on Intranasal Spray Deposition

Abstract

This study investigated the intricate dynamics of intranasal spray deposition within nasal models, considering variations in head orientation and stages of the nasal cycle. Employing controlled delivery conditions, we compared the deposition patterns of saline nasal sprays in models representing congestion (N1), normal (N0), and decongestion (P1, P2) during one nasal cycle. The results highlighted the impact of the nasal cycle on spray distribution, with congestion leading to confined deposition and decongestion allowing for broader dispersion of spray droplets and increased sedimentation towards the posterior turbinate. In particular, the progressive nasal dilation from N1 to P2 decreased the spray deposition in the middle turbinate. The head angle, in conjunction with the nasal cycle, significantly influenced the nasal spray deposition distribution, affecting targeted drug delivery within the nasal cavity. Despite controlled parameters, a notable variance in deposition was observed, emphasizing the complex interplay of gravity, flow shear, nasal cycle, and nasal morphology. The magnitude of variance increased as the head tilt angle increased backward from upright to 22.5° to 45° due to increasing gravity and liquid film destabilization, especially under decongestion conditions (P1, P2). This study's findings underscore the importance of considering both natural physiological variations and head orientation in optimizing intranasal drug delivery.

Keywords: decongestion; deposition patterns; intranasal spray deposition; nasal congestion; nasal cycle; nasal morphology; nasal resistance; targeted drug delivery; turbinate.

Figure 1

Variation in the left inferior meatus due to concha (turbinate) congestion/decongestion (N1–P2) within one nasal cycle: (a) diagram of nasal anatomy, (b) visualization of a selected cross section among N1–P2, (c) quantification of the cross-sectional area variation among N1–P2 in the turbinate region, and (d) turbinate morphological variation among N1–P2. N1: the left inferior meatus shrinks due to concha congestion; N0: normal; P1 and P2: the left inferior meatus dilates due to increasing concha decongestion.

Figure 2

Nasal casts and experimental setup: (a) Nasal cast sections (front nose, T1, T2, T3, and nasopharynx [NP]) for deposition quantification. (b) Sectional views of the turbinate region sections of the four nasal casts (N1, N0, P1, and P2) illustrating varying inferior turbinate thickness. (c) Experimental setup depicting three head positions: upright, 22.5°, and 45° back tilts.

Figure 3

Time series visualization of droplet distribution, liquid film development, and translocation in the N1 model with a 22.5° backward tilt following: (a) a single spray pump dose and (b) two doses of spray applications.

Figure 4

Liquid drop and film deposition within the various models with a 22.5° backward head tilt: (a) after one dose of spray application, (b) after two doses, and (c) after two doses captured from the septum side of each model.

Figure 5

Liquid drop and film deposition within the various models after two doses of spray application with an (a) upright (0°) head angle and (b) 45° backward head tilt. The upper and lower panels in (a,b) are views from the lateral and septum side, respectively.

Figure 6

Deposition variation vs. nasal cycle (N1, N0, P1, and P2) in different regions of the nose with an upright head position: (a) front nose, (b) T1, (c) T2, and (d) T3.

Figure 7

Deposition variation vs. nasal cycle (N1, N0, P1, and P2) in different regions of the nose with a 22.5° back tilt head position: (a) front nose, (b) T1, (c) T2, and (d) T3.

Figure 8

Deposition variation vs. nasal cycle (N1, N0, P1, and P2) in different regions of the nose with a 45° back tilt head position: (a) front nose, (b) T1, (c) T2, and (d) T3.

Figure 9

The violin and mean plots of the total deposited mass in four nasal models (N1–P2) and three head orientations: (a) head angle effect and (b) nasal dilation effect.

Figure 10

Factorial analyses vs. head angle for regional deposition in four nasal models (N1–P2): (a) mean plot and (b) violin plot.

Figure 11

Factorial analyses vs. nasal cycle for regional deposition with three head orientations: (a) mean plot vs. nasal dilation and (b) violin plot.